Heart failure (HF) is a syndrome with global clinical and socioeconomic burden worldwide owing to its poor prognosis. Accumulating evidence has implicated the possible contribution of gut microbiota-derived metabolites, short-chain fatty acids (SCFAs), on the pathology of a variety of diseases. The changes of SCFA concentration were reported to be observed in various cardiovascular diseases including HF in experimental animals and humans. HF causes hypoperfusion and/or congestion in the gut, which may lead to lowered production of SCFAs, possibly through the pathological changes of the gut microenvironment including microbiota composition. Recent studies suggest that SCFAs may play a significant role in the pathology of HF, possibly through an agonistic effect on G-protein-coupled receptors, histone deacetylases (HDACs) inhibition, restoration of mitochondrial function, amelioration of cardiac inflammatory response, its utilization as an energy source, and remote effect attributable to a protective effect on the other organs. Collectively, in the pathology of HF, SCFAs might play a significant role as a key mediator in the gut–heart axis. However, these possible mechanisms have not been entirely clarified and need further investigation.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) show cardiovascular protective effects, regardless of the patient’s history of diabetes mellitus (DM). SGLT2is suppressed cardiovascular adverse events in patients with type 2 DM, and furthermore, SGLT-2is reduced the risk of worsening heart failure (HF) events or cardiovascular death in patients with HF. Along with these research findings, SGLT-2is are recommended for patients with HF in the latest guidelines. Despite these benefits, the concern surrounding the increasing risk of body weight loss and other adverse events has not yet been resolved, especially for patients with sarcopenia or frailty. The DAPA-HF and DELIVER trials consistently showed the efficacy and safety of SGLT-2i for HF patients with frailty. However, the Rockwood frailty index that derived from a cumulative deficit model was employed for frailty assessment in these trials, which might not be suitable for the evaluation of physical frailty or sarcopenia alone. There is no fixed consensus on which evaluation tool to use or its cutoff value for the diagnosis and assessment of frailty in HF patients, or which patients can receive SGLT-2i safely. In this review, we summarize the methodology of frailty assessment and discuss the efficacy and safety of SGLT-2i for HF patients with sarcopenia or frailty.

A wide range of anti-myocardial autoantibodies have been reported since the 1970s. Among them, autoantibodies against the β₁-adrenergic receptor (β₁AR-AAb) have been the most thoroughly investigated, especially in dilated cardiomyopathy (DCM). Β₁AR-Aabs have agonist effects inducing desensitization of β₁AR, cardiomyocyte apoptosis, and sustained calcium influx which lead to cardiac dysfunction and arrhythmias. Β₁AR-Aab has been reported to be detected in approximately 40% of patients with DCM, and the presence of the antibody has been associated with worse clinical outcomes. The removal of anti-myocardial autoantibodies including β₁AR-AAb by immunoadsorption is beneficial for the improvement of cardiac function for DCM patients. However, several studies have suggested that its efficacy depended on the removal of AAbs belonging to the IgG3 subclass, not total IgG. IgG subclasses differ in the structure of the Fc region, suggesting that the mechanism of action of β₁AR-AAb differs depending on the IgG subclasses. Our previous clinical research demonstrated that the patients with β₁AR-AAb better responded to β-blocker therapy, but the following studies found that its response also differed among IgG subclasses. Further studies are needed to elucidate the possible pathogenic role of IgG subclasses of β1AR-AAbs in DCM, and the broad spectrum of cardiovascular diseases including HF with preserved ejection fraction.

Biological sex is one of the major factors characterizing the heart failure (HF) patient phenotype. Understanding sex-related differences in HF is crucial to implement personalized care for HF patients with various phenotypes. There are sex differences in left ventricular (LV) remodeling patterns in the HF setting, namely, more likely concentric remodeling and diastolic dysfunction in women and eccentric remodeling and systolic dysfunction in men. Recently supra-normal EF (snLVEF) has been recognized as a risk of worse outcome. This pathology might be more relevant in female patients. The possible mechanism may be through coronary microvascular dysfunction and sympathetic nerve overactivation from the findings of previous studies. Further, estrogen deficit might play a significant role in this pathophysiology. The sex difference in body composition may also be related to the difference in LV remodeling and outcome. Lower implementation in guideline-directed medical therapy (GDMT) in female HFrEF patients might also be one of the factors related to sex differences in relation to outcomes. In this review, we will discuss the sex differences in cardiac and clinical phenotypes and their relation to outcomes in HF patients and further discuss how to provide appropriate treatment strategies for female patients.

Venous thromboembolism (VTE) is a common comorbidity of cancer, often referred to as cancer-associated thrombosis (CAT). Even though its prevalence has been increasing, its clinical picture has not been thoroughly investigated. In this single-center retrospective observational study, 259 patients who were treated for pulmonary embolism (PE) between January 2015 and December 2020 were available for analysis. The patients were divided by the presence or absence of concomitant malignancy, and those with malignancy (N = 120, 46%) were further classified into active (N = 40, 15%) and inactive groups according to the treatment status of malignancy. In patients with malignancy, PE was more often diagnosed incidentally by computed tomography or D-dimer testing, and the proportion of massive PE was lower. Although D-dimer levels overall decreased after the initiation of anticoagulation therapy, concomitant malignancy was independently associated with higher D-dimer at discharge despite the lower severity of PE at onset. The patients with malignancy had a poor prognosis during post-discharge follow-up. Active malignancy was independently associated with major adverse cardiovascular events (MACE) and major bleeding. D-dimer at discharge was an independent predictor of mortality even after adjustment for malignancy. This study’s findings suggest that CAT-PE patients might have hypercoagulable states, which can potentially lead to a poorer prognosis.

Background: SGLT2 (sodium–glucose cotransporter‐2) inhibitors (SGLT2is) improve outcomes in heart failure (HF), but evidence in patients with frailty and acute HF (AHF) is limited. This study investigated the association between SGLT2i use at discharge and outcomes in patients with AHF, with a focus on frailty. Methods: We analyzed 5579 patients hospitalized for AHF enrolled between 2018 and 2024 in the prospective WET‐HF2 (West Tokyo Heart Failure 2) registry in Japan (age 79 years, 43% women, body mass index 23.1, 23% ischemic cause, left ventricular ejection fraction 45%, 24% SGLT2is at discharge). Frailty was assessed using the Clinical Frailty Scale (≥4; 63%), and complementary analyses were performed using frailty‐related factors (low body mass index, reduced activities of daily living, malnutrition, and dementia). The primary outcome was a composite of cardiac death or HF rehospitalization within 1 year, which occurred in 766 patients (18%). A propensity score was calculated using variables associated with SGLT2i prescription. Results: After propensity score–based inverse probability of treatment weighting adjustment, SGLT2i use was associated with a lower risk of the primary outcome (hazard ratio [HR], 0.76, P =0.045). This association was more pronounced in patients with frailty (HR, 0.59, P =0.005), but not in patients without frailty (HR, 1.18; P _interaction =0.010). Analyses using frailty‐related factors yielded similar patterns. At 1 year, SGLT2i use at discharge was not associated with deterioration in body mass index or nutritional status. Conclusions: In this observational registry, SGLT2i use at discharge was associated with improved outcomes in patients with AHF, particularly those with frailty, without evidence of nutritional harm. These findings support the potential safety of SGLT2is in patients with frailty and AHF.